EBV monitoring after liver transplant may help reduce incidence of PTLD

Monitoring Epstein-Barr virus (EBV) viral load after liver transplant in adults may help reduce incidence of post-transplant lymphoproliferative disease (PTLD), a retrospective study found.

While an EBV-DNA viral load monitoring strategy, including the reduction of immunosuppression, has led to a lower incidence of PTLD in pediatric patients, its effectiveness in adults is unknown, the researchers noted. They examined effects of the strategy on the incidence of PTLD after liver transplant in adults at two university medical centers in the Netherlands. Adult recipients of first liver transplant in Leiden between September 2003 and January 2017 with an EBV viral load monitoring strategy comprised the monitoring group (M1), recipients of first liver transplant in Rotterdam between January 2003 and January 2017 without such a strategy comprised the contemporary control group (C1), and those who had transplants in Leiden between September 1992 and September 2003 or in Rotterdam between 1986 and January 2003 comprised the historical control groups (M0 and C0, respectively).

Under the EBV monitoring strategy, all consecutive liver transplant recipients in Leiden had weekly monitoring during the first month, biweekly monitoring in the second month, and then monthly monitoring or at additional visits until one year after transplant. According to the protocol, in the case of two measurable EBV viral loads within two months during the first year after liver transplant, immunosuppression should be reduced by dose reduction of the calcineurin inhibitor and/or dose reduction or cessation of mycophenolate mofetil, azathioprine, or prednisolone if possible. If EBV viral load did not decrease, further reduction of immunosuppression was required. With further persistence of EBV viral load positivity, one dose of 375 mg/m² IV anti-CD20 (rituximab) was administered while immunosuppression was temporarily continued with only low-dose prednisolone. The primary outcome was cumulative incidence of PTLD, corrected for possible confounders. Results were published Jan. 17 by Annals of Internal Medicine.

A total of 1,281 consecutive patients with at least two weeks of follow-up were included in the study. The crude PTLD incidence rates for the four groups were 1 per 2,228.9 person-years in the M1 group, 10 per 4,143.5 person-years in group C1, 8 per 1,289.9 person-years in group M0, and 10 per 3,611.8 person-years in group C0. Of the 29 PTLD cases, 14 were EBV related, eight were not EBV related, and in seven the relationship to EBV was unknown. A difference-in-differences analysis showed a numerically larger within-hospital decrease in PTLD over time in the hospital that used the monitoring strategy compared with the hospital that did not use the strategy. In an inverse probability of treatment-weighted analysis, monitoring showed the most favorable outcome at 15-year follow-up, with an estimated 70.6 fewer PTLD cases (95% CI, −61.7 to 202.9) per 1,000 patients, although this interval included the null value of 0.

Among other limitations, the level of EBV viral load above which action is warranted has not been well established, the study authors noted. They added that the number of outcome events was limited, lowering the study's statistical power. “Despite these limitations, we strongly believe that the reported results merit serious consideration of the EBV [viral load] monitoring policy in an attempt to reduce the incidence of PTLD after [liver transplant] in adults,” the authors wrote. “At least such a strategy seems safe.”